Sensory neuroscience offers a rich class of challenges of multi- disciplinary approaches to scientific investigation, in which all levels of analysis, from molecular to systems approaches, can be related to cognitive perceptual events. We propose to create a multi-disciplinary Center for Biomedical Research Excellence in Sensory Neuroscience whose members combined their collective experience to solve basic scientific problems that bear on development of treatments for human disease. Five research projects are proposed that are centered on the topics of development and plasticity. Techniques ranging from genetic to functional brain imaging analysis of congenital and developmental sensory disorders, and combined anatomical, physiological and molecular analyses of developing neurons in vitro are proposed. These studies are aimed at important and timely topics in sensory neurobiology and utilize both animal and human, including pediatric subjects. Project #1 investigates the genetic basis for Usher's syndrome, a congenital disorder of hearing and balance. Project #2 utilizes functional brain imaging to characterize central deficits in Amybylopia in adults and children and to define and evaluate new treatment strategies. Project #3 investigates the structural basis for axonal pathfinding to innervate appropriate targets during development of the central auditory system. Project #4 evaluates the role of calcium signaling and neural transmission in the formation and stabilization of synaptic contacts. Project #5 identifies molecular signals that guide formation of tonotopic, or frequency organization of auditory system cell groups. Four of the five proposed projects have passed merit review at NIH and were recommended for funding using small grant mechanisms. The proposed center forges ties between our state's two medical schools and occurs at a strategic time when both institutions are investing in expansion of their neuroscience research enterprise. This group of sensory neuroscientists has reached a critical mass and, with the faculty expansion and research support requested herein, will have the support to become a unique resource of international distinction. Upon awarding of this COBRE, the West Virginia School of Medicine will relocate the entire contingent of WFVU COBRE scientists to redesigned and completely renovated laboratory space during the term of funding Marshall University School of Medicine pledges to expand and renovate COBRE lab space when funded.